The overall objective of this research project is to examine the molecular factors that influence the pathogenesis of immune complex glomerulonephritis. The role of immunoglobulin class in producing focal glomerulosclerosis was evaluated in a rabbit model of IgG and IgM immune complex glomerulonephritis. IgM was found to not have any unique biological effect on glomerular histology and did not produce focal glomerulosclerosis. The role of electrical charge as a determinant of glomerular immune complex localization was investigated in both the rabbit and rat. It was found in both species that the administration of a cationic antigen resulted in a significantly different renal lesion than did the anionic antigen. In the rat the cationic antigen produced a mesangial immune complex glomerulonephritis, whereas the anionic antigen induced principally capillary wall deposits. The administration of aminonucleoside of puromycin had litle effect on the immune deposits. The administration of cationic BSA to the rabbit induced a uniform lesion of pure membranous nephropathy. Experiments showed that the cationic antigen was capable of direct glomerular binding. It is postulated that the cationic antigen predisposed to in situ immune complex formation and this is the pathogenic mechanism of membranous nephropathy in this model. Electrical charge is emerging as an important new factor in immune complex glomerulonephritis and this project will continue to explore the role of electrical charge in the coming year.